Oncology

Summary of cancer treatments

  • Treatment of head and neck cancers
    • Cancer of oral cavity -> surgery, adjuvant RT or RCT if high-risk features
    • Cancer of pharynx
      • Nasopharynx -> RCT
      • Oropharynx -> RCT/surgery
      • Hypopharynx -> surgery
    • Cancer of larynx
      • Early cancer -> RT/surgery
      • Locally advanced cancer -> RCT/total laryngectomy
      • Advanced cancer -> total laryngectomy + adjuvant RT
    • Stage III and IV head and neck cancers -> RCT/radiobiotherapy
  • Treatment of NSCLC
    • Stage I – IIIa -> surgery ± adjuvant CT
    • Stage IIIb -> RCT
    • Stage IIIc – IV
      • Squamous cell carcinoma -> polychemotherapy ± immunotherapy
      • Adenocarcinoma -> targeted therapy against EGFR, ALK, ROS
  • Treatment of SCLC
    • Limited disease -> RCT + prophylactic cranial irradiation if remission is achieved
    • Extensive disease -> CT + prophylactic cranial irradiation in most cases
  • Treatment of breast cancer
    • Early breast cancer
      • Without BRCA mutation -> breast-conserving surgery + adjuvant RT
      • With BRCA mutation -> Mastectomy + prophylactic contralateral mastectomy + prophylactic bilateral salpingo-oopherectomy
    • For locally advanced breast cancer -> neoadjuvant systemic therapy + surgery + adjuvant systemic therapy
    • For metastatic breast cancer -> neoadjuvant systemic therapy + surgery and/or RT
      • With BRCA mutation -> PARP inhibitors
  • Treatment of oesophageal cancer
    • Localized disease -> neoadjuvant CT/RCT + surgery + adjuvant CT
    • Advanced disease -> RCT/targeted/immunotherapy
  • Treatment of gastric cancer
    • Localized disease -> neoadjuvant CT/RCT + surgery + adjuvant CT/RCT
    • Advanced disease -> neoadjuvant CT + surgery + adjuvant CT ± targeted/immunotherapy
  • Treatment of pancreatic cancer
    • Resectable disease -> surgery + adjuvant CT/RCT
    • Non-resectable disease -> CT ± palliative surgery
  • Treatment of HCC
    • Very early or early stage -> Surgery
    • Early stage -> Liver transplant
    • Intermediate stage -> TACE
    • Advanced stage -> Sorafenib
    • Terminal stage -> Palliative
  • Treatment of CRC
    • Stage I -> Surgery
    • Stage II, III -> Surgery + adjuvant CT
    • Stage IV -> Palliative
  • Treatment of non-melanoma skin cc (BCC, SCC) -> surgery
  • Treatment of melanoma
    • Localized disease -> surgery
    • Regional and metastatic disease -> surgery + adjuvant targeted/immuno
  • Treatment of CNS tumours
    • Low-grade glioma -> surgery
    • High-grade glioma -> surgery + RCT (temozolomide)
    • Multiple brain mets -> whole brain radiotherapy
    • Primary CNS lymphoma -> CT (methotrexate)
  • Treatment of ovarian cancer
    • Stage I, II -> surgery + adjuvant CT
    • Stage III, IV -> cytoreduction + adjuvant CT
  • Treatment of cervical cancer
    • Early cervical disease -> surgery/RT ± adjuvant RCT
    • Locally advanced disease -> RCT
    • Metastatic disease -> Palliative
  • Treatment of endometrial cancer
    • Stage I, II -> Surgery + adjuvant RT
    • Stage III, IV -> Cytoreduction + adjuvant CT/RT/hormonal
  • Treatment of prostate cancer
    • Low and intermediate risk localized disease -> Observation/surgery/RT
    • High-risk localized and locally advanced disease -> [ADT + ERBT] or surgery
    • Hormone-naive metastatic disease -> ADT + antiandrogens
    • Castration-resistant metastatic disease -> ADT + antiandrogens + CT/immunotherapy
  • Treatment of bladder cancer
    • Non-muscle-invasive disease -> TUR-B + intravesical BCG or chemo
    • Muscle-invasive disease -> surgery or [TUR-B + RCT]
    • Metastatic disease -> palliative
  • Treatment of RCC
    • Localized disease -> surgery
    • Metastatic disease -> targeted/immunotherapy
  • Treatment of testicular cancer
    • Localized disease -> observation or [orchidectomy + adjuvant CT]
    • Locally advanced disease -> orchidectomy + adjuvant RT/CT/RPLND
    • Metastatic disease -> orchidectomy + adjuvant CT

Introduction to oncology

  • https://www.cancer.org/ is a surprisingly good source for information on the specific malignancies. They explain specific procedures, staging, diagnosis and treatment of all cancers. If there’s something which you don’t understand, I recommend you check there
  • Epidemiology
    • Most frequent cancers (USA)
      • (Except skin cancer, which is the most common)
      • Prostate/breast
      • Lung and bronchus
      • Colorectal
    • Cancers causing the most deaths (USA)
      • Lung and bronchus
      • Prostate/breast
      • Colorectal
  • The clinical courses of cancer patients
    • The absolute cure rate is 60%
    • 30% survive several years
    • 10% experience no real effect of treatment
  • CAUTION – cancer’s seven warning signs
    • Change in bowel or bladder habits
    • A sore that does not heal
    • Unusual bleeding or discharge
    • Thickening of lump in breast or elsewhere
    • Indigestion or difficulty in swallowing
    • Obvious change in wart or mole
    • Nagging cough or hoarseness
  • Grading
    • Grading is based on how differentiated the tumor is on histology, compared to healthy tissue
    • From G1 (well differentiated) to G4 (very poorly differentiated)
    • Special grading systems
      • Gleason score – for prostate cancer
    • Grading also takes into account:
      • The degree of vessel penetration
      • Presence of hormonal receptors or growth factor receptors
      • Presence of certain gene mutations
  • Staging
    • TNM staging system is often used
      • Brain tumours and haematological malignancies use other systems
    • Clinical staging (cTNM) – staging based on the clinical information (obtained before surgery)
      • Including physical examination, blood tests, imaging, biopsy, endoscopy, etc.
      • Histopathological examination of biopsy is performed for most cancers
    • Pathological staging (pTNM) – staging based on the clinical information + information from the pathologist after surgical resection
      • Some cancers are not treated surgically, so there will be no pTNM stage, only cTNM stage
      • Many tumours are examined histopathologically twice – once of the biopsy taken before surgery, and once of the tumour which was removed during surgery
    • Treatment-associated staging (yTNM) – staging after chemotherapy and/or radiation therapy
    • Generally:
      • Stages I and II are referred to as “early” or “non-invasive” disease
      • Stage III is referred to as “locally” or “regionally” “advanced” or “invasive” disease
      • Stage IV is referred to as “advanced” or “metastatic” disease
  • Prognostic factors
    • Those factors which determine the patient’s prognosis
    • Most important factors
      • Grading
      • Staging
      • Performance status
        • Different performance status scales exist
        • Eastern Cooperative Oncology Group performance status (ECOG PS)
          • Grade 0 – Fully active, no restriction on daily activity
          • Grade 4 – Completely disabled, not capable of self-care, totally confined to bed or chair
          • Grade 5 – dead
        • Karnofsky performance scale (KPS)
          • 100 – normal
          • 0 – dead
    • Other factors
      • Age
      • The excess of weight loss
      • The localization of the disease
  • Predictive factors
    • Those factors which are associated with response or lack of response to a particular therapy
      • For example, the presence of oestrogen receptors in breast cancer is a predictive factor, as it predicts the patient’s response to antioestrogens
    • Many predictive factors are also prognostic factors
  • Oncological teams
    • Cancers patients are treated by oncological teams rather than individual oncologists
    • This:
      • Optimizes treatments
      • Allows learning from each other
      • Allows teamwork across multiple modalities (pathology, radiology, etc.)
      • Allows responsibility to be shared
      • Allows members of the team to support each other
    • Includes
      • Oncologists
      • Pathologists
      • Radiologists
      • Nurses
      • Etc.
  • Treatment
    • Cancer treatment doesn’t begin until the staging is complete, unless
      • The cancer is causing urgent, life-threatening complications
      • Complete staging is impossible or too dangerous (certain brain tumours)
    • Important factors in treatment decision
      • Performance status
      • Renal function
      • Liver function
      • Bone marrow function
    • Types of therapy
      • Curative therapy – therapy with the intent of curing the cancer
      • Palliative therapy – therapy with the intent of relieving symptoms and improving quality of life
      • Neoadjuvant therapy – chemo and/or radiation before surgery
        • Neoadjuvant therapy can reduce the tumour size, making surgery more likely to be curative
      • Adjuvant therapy – chemo and/or radiation after surgery
    • Modalities
      • Surgery – in 60% of cases
      • Radiotherapy – in 30% of cases
      • Medical therapy – in 10% of cases
      • Modalities are generally combined
        • Radiochemotherapy refers to simultaneous use of radio and chemo, as opposed to radio first and then chemo after
    • Treatment response
      • Complete response/regression (CR) – no evidence of tumour after a certain amount of time
      • Partial response/regression (PR) – decrease in tumour volume
      • Stable disease (SD) – minimal decrease or increase in tumour volume
      • Progressive disease (PD) – increase in tumour volume

1. The basic principles of tumor biology

  • Etiological factors contributing to cancer development
    • Environmental exposure
      • Asbestos -> mesothelioma, RCC
      • Formaldehyde -> nose and nasopharyngeal cc
    • Radiation
      • Those with childhood leukaemia often develop solid tumours 10 – 20 years after the radiotherapy
    • Lifestyle problems
      • Smoking -> lung cancer, head and neck cancer
      • Alcohol -> head and neck cancer, oesophageal cancer
    • Alimentary factors
      • Obesity, diabetes -> CRC
    • Hygienic problems
      • -> cancer of glans penis
    • Infections
      • HPV -> cervical cc
      • EBV -> nasopharyngeal carcinoma
      • Aflatoxin -> HCC
    • Hormonal effects
      • Oestrogen -> breast cc, endometrial cc
      • Testosterone -> prostate cc
    • Genetic background
      • BCL/ABL => CML
      • APC => CRC
  • Biological factors contributing to cancer development
    • Trouble in communication between cells
    • Absence of contact inhibition
    • Uncontrolled growth and cell dividing
    • Omitting the integrity of neighbouring cells, tissues and organs
    • Neo-vascularization and aberrant blood vessels
    • The possibility of penetrating blood vessels
    • Disturbing the metabolic activity of the organ
    • Evolving paraneoplastic symptoms

2. Principles of surgical oncology

  • Debulking and cytoreduction
    • Debulking or cytoreduction = surgically removing as much of a tumour as possible, in cases where the whole tumour cannot be removed
    • Debulking can be performed palliatively, to increase survival, or with curative intent, by increasing the penetration of adjuvant radiation and/or chemo into the tumour
    • Performed in ovarian cc, endometrial cc, etc.
  • En-bloc resection
    • The entire tumour and a continous layer of healthy tissue around it is removed together
  • Surgical margin
    • During surgery, the margin of the removed tissue is marked with ink
    • While the surgeons wait the pathologist will make frozen slides of the removed tissue and examine it histologically
    • By using the ink as a reference, the pathologist can determine whether the surgery removed all of the tumour or not
    • If the surgical margin is clear/negative/clean, there are no tumour cells at the margin, so further treatment is usually not needed
    • If the surgical margin is positive, more surgery or other adjuvant treatment is needed to ensure that no tumour cells remain
    • R0 resection – complete resection of the tumour
      • No macroscopic evidence of tumour, with negative margins
    • R1 resection – microscopic remnants of tumour remain
      • No macroscopic evidence of tumour, but positive margins
    • R2 resection – macroscopic remnants of tumour remain
  • Preoperative (neoadjuvant) and postoperative (adjuvant) therapy
    • For some cancers clinical studies have established that neoadjuvant and/or adjuvant therapy is beneficial
    • In some cases, postoperative therapy is only indicated if certain features of the tumour are discovered during surgery (during pathological staging), like
      • Incomplete (R1, R2) surgical resection
      • Spread to lymph nodes
      • Certain mutations
      • Very deep invasion
      • Etc.
      • These are features which are associated with high risk of recurrence or poor prognosis
    • Postoperative therapy can be chemo, radio, radiochemotherapy, etc.

3. Radiation physics

  • Types of radiation used
    • Natural radiation (due to radioactive decay)
      • Alpha radiation (two protons and two neutrons)
      • Beta radiation (high-energy electrons)
        • Electrons (beta radiation) has low penetration power, so beta radiation is only suitable for treating tumours near the skin surface
    • Gamma radiation (high-energy photons)
      • Photon radiation (gamma and X-ray radiation) has high penetration power, so it is suitable for treating deep tumours
    • Artificial radiation
      • X-rays (gamma radiation which is artificially made)
      • Heavy ion radiation
        • Heavy ions, like carbon ions, are accelerated to high speeds
        • Proton radiation (alpha radiation) and heavy-ion radiation don’t penetrate tissues deeper than a certain point
          • This makes these types of radiation suitable for treating tumours where radiation-sensitive tissue is very close, for example inside the skull
          • They’re also suitable for treating tumours close to the skin
          • This effect is due to the so-called “Bragg peak” on the percentage depth dose distribution
  • Particle therapy
    • Accelerated protons or heavy ions are sent into the tumour
    • Very expensive
  • Compton-scattering is the most important radiation effect on tissues in radiotherapy
    • The photoelectric effect, pair production and coherent scattering are less important
  • The inverse square law
    • The law states that the intensity of radiation decreases in an inverse square ratio with the distance from the source of the radiation
    • For example
      • If the distance from the source is doubled, the radiation intensity is reduced to one fourth
      • If the distance from the source is increased three-fold, the radiation intensity is reduced to one ninth
    • The inverse square law is important in treatment planning in brachytherapy
  • Percentage depth dose (PDD)
    • The PDD is the percentage of the maximum dose which is deposited in tissue (or something, it’s confusing)
    • PDD is important in treatment planning in teletherapy
  • Squamous cell cancers are generally very radiosensitive
    • Adenocarcinomas on the other hand, are not
  • Radiation biology
    • Radiation induces double-stranded breaks in DNA
    • The cell is most sensitive to radiation in the M and G2 phases of the cell cycle
    • The oxygen effect
      • According to the oxygen effect, normoxic tissues and cells are more radiosenstive than hypoxic ones
      • The oxygen effect occurs because oxygen “stabilizes” or “makes permanent” the DNA damage produced by reactive oxygen species
      • In hypoxic tissues, the DNA damage is not made permanent and can therefore be repaired by the cell

4. The equipment used in radiation oncology

  • Types of radiotherapy
    • External beam radiation therapy (EBRT)/teletherapy
      • The radiation source is outside the patient
      • The source can be rotated around the patient, allowing the radiation beam to target the tumour from a variety of directions
      • Types
        • Conventional external beam therapy
        • Three-dimensional conformal radiotherapy (3DCRT)
        • Intensity modulated radiation therapy (IMRT)
        • Stereotactic radiosurgery/radiotherapy
    • A multileaf collimator (MLC) is used to shape the radiation beam
      • Especially used in IMRT and 3DCRT
    • Internal radiation therapy/brachytherapy
      • The radiation source is inside or very close to the patient, as close to the tumour as possible, or even inside the tumour
      • Can be temporary or permanent
        • Temporary brachytherapy – the radiation source is placed and then removed after some time
          • Most common
        • Permanent brachytherapy – a small radiation source is permanently placed into the patient
          • Also called “seed implantation”
          • The radioactive “seed” loses its radioactivity after some months, but won’t be removed
      • Can be high dose-rate (HDR), low dose-rate (LDR) or pulsed dose-rate (PDR)
        • HDR reduces the treatment time, and is most commonly used
        • HDR = dose rate of more than 12 Gy per hour
          • Treatment typically lasts a few minutes
        • LDR = dose rate of less than 2 Gy per hour
          • Treatment typically lasts 24 hours
        • PDR = short pulses of radiation are given
          • Treatment typically lasts 24 hours
      • Types
        • Intracavital brachytherapy
          • Into the cervix, bronchi, etc.
        • Interstitial brachytherapy
          • Into the breast, prostate, etc.
    • Systematic radiation therapy
      • An isotope is injected into the patient, by itself or attached to a specific molecule
      • The isotope will travel to the tumour and irradiate it from inside
      • The isotope often gives off alpha or beta-waves, as these waves don’t travel far in the body
        • Alpha waves only travel 100 µm
      • Examples
        • Radioactive iodine given for thyroid cancer
        • Radium-223 given for bone metastases
  • Equipment used in brachytherapy
    • Afterloading
      • The technique where a machine (an afterloader) is used to deliver the radiation source into the patient during brachytherapy
      • This eliminates the need for a person to deliver the radiation source, eliminating radiation exposure for that person
        • Manual delivery of brachytherapy is seldom used for this reason
      • Often used with HDR, sometimes called HDR Afterloading
      • 192Iridium is often used as radiation source
  • Equipment used in teletherapy
    • Cobalt unit
      • Older type of teletherapy
      • The external beam is generated using 60Cobalt
    • Linear accelerator (LINAC)
      • More modern than cobalt unit
      • Most commonly used device for external beam radiation therapy
      • The external beam is generated using linear acceleration
      • A multileaf collimator allows precise modification of the radiation field
      • Used for stereotactic surgery, intensity modulated radiotherapy, particle therapy etc.
    • Gamma knife
      • Used for stereotactic radiosurgery in the brain
    • Tomotherapy
    • CyberKnife

5. Treatment planning, radiation protection

  • Treatment planning
    • Imaging is used to form a virtual model of the patient, including the tumour
      • Native CT is almost always used, because the physical interactions between the radiation and the tissue is the same in native CT as in radiotherapy
        • This means that a native CT contains the dose-absorbing properties of the tissues of the patient
      • By using image registration and image fusion, multiple imaging modelities may be combined, if needed
        • Image registration refers to “matching” multiple imaging modalities by mapping the coordinates of anatomical structures on the different modalities, so that they “match” on top of each other
        • Image fusion refers to displaying multiple modalities on top of each other after image registration
        • MRI provides good differentiation between different soft tissues
        • PET provides good information of functionality and metastases
        • Ultrasound cannot be used for treatment planning
    • Computer systems allow for simulation and calculation of how different radiotherapy approaches would deliver radiation to the tumour and the surrounding tissues
    • Modern techniques allow for even more precise radiation planning
      • Intensity-modulated radiation therapy (IMRT)
      • 3D conformal radiation therapy (3DCRT)
      • Intensity-modulated arc therapy (IMAT)
      • Image-guided radiation therapy (IGRT)
    • Volumes in radiotheapy planning
      • Gross tumour volume (GTV) = the volume of the macroscopic tumour
      • Clinical target volume (CTV) = the GTV + microscopic, un-imageable tumour spread
      • Planning target volume (PTV) = the CTV + uncertainties in planning or delivery
  • Fractionation of radiation therapy
    • Most cancers respond based on the total (cumulative) amount of radiation, not the size of the individual doses
      • However, side effects are mostly related to the sizes of the individual doses
    • As such, the sizes of the doses can be increased or decreased
    • Hypofractionated radiation therapy
      • When the total dose of radiation is divided into larger but fewer doses
      • Used for cancers which are sensitive to large individual radiation doses
      • Treatment course is completed quicker
      • Often used in breast cancer and prostate cancer
    • Hyperfractionated radiation therapy
      • When the total dose of radiation is divided into smaller but more doses, often given more than once a day
      • May produce fewer side effects
      • Used for cancers with high turnover, like SCLC

6. Basic concepts of chemotherapy

  • Polychemotherapy = simultaneous use of multiple chemo drugs
    • The term is not consistently used, even by me
    • Recently, we have moved from preferring to use multiple chemo drugs, so the term is kind of reduntant
  • Mode of actions
    • Induce DNA damage
    • Inhibit DNA repair mechanisms
    • Inhibit metabolism
      • For example nucleotide synthesis
    • Inhibit mitosis
    • Inhibit neo-vascularization
  • Commonly used drugs
    • Platinum-based drugs
      • Cisplatin
        • Very nephrotoxic – renal function must be measured before use
      • Carboplatin
        • Less nephrotoxic – sometimes used as an alternative to cisplatin in case of poor kidney function
    • 5-FU
    • Taxanes
      • Paclitaxel
      • Docetaxel
  • Commonly used regimens
    • FLOT
      • 5-FU
      • Leucovorin
      • Oxaliplatin
      • DoceTaxel
    • FOLFOX
      • FOLinic acid (leucovorin)
      • 5-FU
      • Oxaliplatin
    • FOLFIRI
      • FOLinic acid
      • 5-FU
      • IRInotecan
    • ECX
      • Epirubicin
      • Cisplatin
      • Capecitabine
    • Gem/cis
      • Gemcitabine + cisplatin
    • XELOX
      • Capecitabine + oxaliplatin

7. Basic concepts of hormone therapy

8. Biological therapy, targeted therapy and immunotherapy

  • Targeted therapy
    • Targeted therapy refers to using drugs which are not cytotoxic but rather specifically target certain molecules
    • Targeted therapy often prolongs survival, sometimes for years, and the patient remains on the targeted therapy during this time
    • Biological therapy
      • = refers to biological drugs, most commonly monoclonal antibodies
      • Bevacizumab – anti-VEGF
        • Inhibits vascular proliferation and therefore neovascularization
      • Cetuximab – anti-EGFR
    • Small molecules
      • = refers to small molecule drugs, which enter the cells and inhibit certain intracellular proteins
      • Gefitinib, erlotinib – EGFR inhibitors
      • Alectinib – ALK inhibitor
      • Vemurafenib – BRAF inhibitor
        • Only works on a certain type of BRAF mutation in melanoma
        • Actually stimulates wildtype BRAF
      • Sorafenib – Multi protein kinase inhibitor
        • Inhibits VEGFR, PDGFR, RAF, etc.
    • Common side effects
      • Anti-EGFR and EGFR inhibitors
        • Acneiform dermatitis
      • Anti-BRAF and BRAF inhibitors
        • Photosensitivity
        • Squamous cell carcinoma
      • Sorafenib
        • Alopecia
        • Hand-foot syndrome
  • Immunotherapy
    • Immune checkpoint inhibitors
      • Most commonly used immunotherapy
      • These drugs are monoclonal antibodies and therefore also technically biological drugs
      • These drugs inhibit the mechanism by which cancer cells inhibit the immune system
      • Anti-PD-1 – nivolumab, pembrolizumab
      • Anti-CTLA-4 – ipilimumab
    • Vaccines
    • Cytokines

9. Cancer pain management

  • Pain -> opioids
  • Nausea -> ondansetron
  • Diarrhoea -> loperamide
  • Phlebitis -> local anti-inflammatory cream

10. Psycho-oncology

11. Oncologic emergencies

  • In case of oncological emergencies oncotherapy can be initiated without knowing the histology of the cancer
  • Increased intracranial pressure
    • Due to brain metastases or primary brain tumor
    • Urgent MRI should be made
    • ASAP treatment includes dexamethasone, forced diuresis (fluid + loop diuretics) and mannitol to reduce oedema
    • Then treat tumor
  • Spinal cord compression
    • Due to enlarging vertebral metastasis or pathologic vertebral fracture due to metastasis
    • Often from breast, lung, prostate, etc.
    • Most often involves thoracic spine
    • X-ray will show blastic or lytic lesions
    • MRi will show localization of spinal cord compression
    • ASAP treatment includes dexamethasone and spinal decompression surgery
    • Then treat tumor
  • Superior vena cava syndrome
    • Can be due to lung cancer, lymphoma etc, but also due to non-cancer conditions (see surgery 1)
    • X-ray will show mediastinal widening
    • CT with contrast will give more detailed picture
    • Hyperfractionated radiation therapy given to provide rapid tumor reduction and symptom relief
  • Malignant pleural effusion
    • Exudate, not transudate
    • Due to tumor cell implants on pleura
    • Due to metastatic breast, lung or lymphoma
    • Chest x-ray shows effusion
    • Thoracentesis shows exudate, also drains fluid
    • Chest tube can be inserted to continually drain fluid
    • Pleurodesis – procedure where the visceral and parietal pleurae are adhered together to prevent fluid accumulation
      • A sclerosing agent like doxycycline, bleomycin or talc is added to the pleural cavity
      • These agents cause the pleurae to adhere to each other
  • Airway obstruction
  • Ileus
  • Hypercalcaemia of malignancy
    • In breast, lung, or multiple myeloma
    • Due to osteolytic metastases, or due to PTH-related peptide secretion
    • Symptoms include fatigue, vomiting, altered mental status
    • Treatment involves hydration and furosemide + bisphosphonates
  • Hyponatraemia
    • Due to syndrome of inappropriate ADH, due to SCLC or other neuroendocrine tumor
    • ASAP slow infusion of hypertonic saline
  • Tumor lysis syndrome
    • Due to chemo of chemosensitive, high cell-turnover tumours, especially leukaemias, lymphomas
    • Massive cell death release causes hyperkalaemia, hyperuricaemia, hyperphosphataemia, secondary hypocalcaemia
    • Prevention is essential, by hydrating patients, possibly giving allopurinol
    • Manifest tumor lysis syndrome may require dialysis
  • Febrile neutropaenia
    • Defined as a single measurement of > 38,3°C oral or a sustained temperature of 38,0°C for 1 hour + neutropaenia (< 500/µL)
    • Take two sets of blood culture ASAP, then immediately start empiric broad-spectrum AB therapy
    • Aminoglycoside + antipseudomonal beta-lactam
  • Disseminated intravascular coagulation
    • Due to acute promyelocytic leukaemia (APML)
    • Signs of haemorrhage and thrombosis
    • All-trans retinoic acid treats APML
    • Replacement of platelets and coagulation factors may be necessary
  • Hyperviscosity syndrome
    • Due to myeloproliferative disease or ALL
    • Hyperviscous blood causes symptoms of impaired microcirculation
    • Treatment includes phlebotomy

12. Palliative care

Specific malignancies template

  • The next topics about specific malignancies will follow this template
  • Epidemiology
  • Etiology
    • Causes, risk factors
  • Pathology
    • Relevant pathological aspects
  • Clinical features
    • Signs and symptoms
  • Stages
    • The clinical and pathological stages. Often based on TNM
    • Sometimes the stages are classified like this
    • Early stage/localized disease
      • The tumour is localized to the primary organ
    • Locally/regionally advanced disease
      • The tumour has spread locally or to local lymph nodes
    • Metastatic/disseminated disease
      • The tumour has spread distally (M1)
  • Risk groups
    • Factors which determine the risk of metastases and poor outcomes
    • Often, these include stage, grade, certain lab markers, certain histological features, etc.
    • The treatment is often based on the risk group
    • Cancers are often divided into low, intermediate and high-risk groups depending on the presence of these factors
    • Age and performance status are important factors for all cancers
  • Diagnosis
    • The process of establishing the diagnosis of cancer
  • Work-up after diagnosis
    • As soon as the diagnosis is established the staging work-up must begin for the clinical staging of the cancer
    • Often includes imaging modalities to evaluate spread and lymph node metastases
    • Can also include tests for biomarkers, biopsy of lymph nodes, etc.
    • NB! It’s common to do MRI of the brain if metastases are present on imaging
    • NB! It’s common to do bone scans if skeletal symptoms are present
  • Treatment
    • Surgery
      • Explains the surgical modalities used, etc.
    • Systemic therapy
      • Chemotherapy
      • Targeted therapy
      • Hormonal therapy
      • Immunotherapy
    • Radiotherapy
    • Treatment according to stage:
    • Early stage/localized disease
    • Locally/regionally advanced disease
    • Metastatic/disseminated disease

13. Tumors of head and neck

  • Tumours of the head and neck include
    • Eye and orbital tumours
    • Oral cavity tumours
    • Pharyngeal tumours
      • Nasopharynx
      • Oropharynx
      • Hypopharynx
    • Laryngeal tumours
      • Supraglottic
      • Glottic
      • Subglottic
    • Tumours of the nasal cavity and paranasal sinuses
    • Tumours of the salivary gland
    • Tumours of the thyroid gland
  • Epidemiology
    • Head and neck cancer is the 6th most common cancer worldwide
  • Etiology
    • Smoking
    • Alcohol
    • Poor oral hygiene
    • EBV – for nasopharyngeal carcinoma
    • HPV – for oropharyngeal and laryngeal cancer
  • Pathology
    • 80% are squamous cell
    • 20% are adenocarcinoma, lymphoma, sarcoma, etc.
    • Precancerous lesions
      • Leukoplakia
      • Erythroplakia
      • Lichen planus
    • Metastasizes most often to lung
  • Clinical features
    • Ulceration of mucosa
    • Exophytic growth of mucosa
    • Neck mass
    • Sore throat
    • Hoarseness
    • Pain radiating into the ear
      • Due to cranial nerve affection
    • Dysphagia
  • Diagnosis
    • FNAB or direct excision biopsy
  • Work-up after diagnosis
    • CT with contrast or MRI of head and neck
    • Laryngoscopy
    • Neck US
    • PET scan
  • Treatment
    • Majority of cases are treated with multiple modalities
    • Surgery
      • Only used if R0 resection with acceptable functional results is expected
        • This means that surgery is not performed unless the surgeon believes that he can completely resect the tumour
      • If early stage cancer -> transoral surgery (TORS)
      • If cancer has spread to lymph nodes, neck dissection must be performed
        • Modified radical neck dissection
        • Selective neck dissection
      • Surgery, especially of pharynx and larynx, impairs quality of life, which must be taken into account when deciding treatment modality
    • Radiotherapy
      • External beam radiotherapy or brachytherapy
      • Can be given with curative or palliative intention
      • Can be given postoperatively or primarily
      • Primary radiotherapy alone is usually sufficient in
        • Cancer of the lip
        • Cancer of the nose
        • Cancer of the floor of the mouth (brachytherapy)
        • Cutaneous lymphoma
    • Chemotherapy
      • Cisplatin
      • Taxanes
      • 5-FU
    • Biological and immunotherapy
      • Cetuximab (anti-EGFR)
      • Nivolumab (anti-PD-1)
      • Pembrolizumab (anti-PD-1)
    • Cancer of oral cavity
      • Surgery
      • Postoperative radiotherapy or radiochemotherapy is indicated if high-risk features are present
        • R1 or R2 resection
        • T3 or T4 tumours
        • Lymph node spread
        • Etc.
      • Before radiotherapy of the oral cavity, dental care is essential
        • Bad teeth etc. can act as a source of inflammation after radiotherapy
    • Cancer of pharynx
      • Nasopharynx is the most radiosensitive, hypopharynx is the least radiosensitive
      • Nasopharyngeal cancer – radiochemotherapy
      • Oropharyngeal cancer – radiochemotherapy is preferred, surgery is option
      • Hypopharyngeal cancer – surgery is preferred, radiochemotherapy is option
    • Cancer of larynx
      • Early cancer – radio or surgery alone
      • Locally advanced cancer – radiochemotherapy or total laryngectomy
      • Advanced cancer – total laryngectomy with adjuvant radiotherapy
    • Stage III and IV
      • Radiochemotherapy or radiobiotherapy
      • With cisplatin or cetuximab, respectively

14. Lung cancer

  • Epidemiology
    • Cancer with the highest mortality rate worldwide
  • Etiology
    • Smoking
      • 80% of lung cancer deaths are due to tobacco use
    • Air pollution
    • Asbestos
  • Clinical features
    • Cough
    • Haemoptysis
    • Dyspnoea
    • Chest pain
    • Extrapulmonary symptoms
      • Superior vena cava syndrome
      • Weight loss
      • etc.
  • Diagnosis
    • If lesions suspicious of tumor is found, biopsy must be taken
    • Acquiring tissue specimens is better than acquiring cytologic specimens
      • As only tissue specimens yield enough material for immunohistochemistry and genetical testing
      • This is important for prognosis and treatment
      • However, cytologic specimen is usually sufficient to determine the histological subtype and to confirm the cancer diagnosis
    • Procedures which yield tissue specimens
      • Endobronchial biopsy or resection
      • Transbronchial biopsy or resection
      • Mediastinoscopy (to biopsy mediastinal nodes or masses)
    • Procedures which yield cytologic specimens
      • Sputum analysis
      • Bronchoalveolar lavage
      • Transthoracic fine needle aspiration biopsy
      • Transbronchial fine needle aspiration biopsy
  • Work-up after diagnosis
    • Contrast CT imaging of chest, liver and adrenal glands
    • PET scan
    • If CT finds metastases (advanced disease), then perform MRI for brain metastases and x-ray/bone scintigraphy for skeletal metastases
    • Lung function test
  • Non-small cell lung cancer (NSCLC)
    • Accounts for 85% of cases
    • Types
      • Adenocarcinoma
        • 40% of cases
        • Idiopathic
        • Peripheral
      • SCC
        • 20% of cases
        • Smoking, etc.
        • Central
      • Large cell carcinoma
        • 10% of cases
        • Peripheral
    • Staging
      • Stage I, II
        • Tumor size < 7 cm
        • No mediastinal invasion
        • No lymph node involvement beyond ipsilateral hilar nodes
        • No distant metastasis (M0)
      • Stage IIIA
        • Tumor size > 7 cm
        • No mediastinal invasion
        • Mediastinal lymph node involvement
        • No distant metastasis (M0)
      • Stage IIIB
        • Any tumor size
        • Mediastinal invasion
        • Distant lymph node spread, but no distant metastasis (M0)
      • Stage IV
        • Any tumour size
        • Any lymph node status
        • Distant metastasis M1
    • Treatment
      • Generally, any tumor stage I – IIIb is potentially curable, while any other stage is palliative
      • Surgery
        • Lobectomy
        • Wedge resection
        • Pneumonectomy
      • Chemotherapy
        • Cisplatin
        • Taxanes (paclitaxel)
      • Radiotherapy
        • External beam therapy and brachytherapy
        • Stereotactic radiotherapy can be used for peripherally located inoperable tumors
        • Emergency indications for radiation
          • Superior vena cava syndrome
          • Malignant spinal cord compression
          • Brain metastasis
      • Targeted therapy
        • EGFR tyrosine kinase inhibitors – erlotinib, gefitinib
        • ALK and ROS inhibitor – crizotinib
        • ALK inhibitor – alectinib
        • Anti-VEGF – bevacizumab
      • Immunotherapy
        • PD-1 inhibitors – pembrolizumab, nivolumab
        • PD-L1 inhibitors – avelumab, atezolizumab, durvalumab
      • Stage I – IIIa
        • Surgery
        • Postoperative chemotherapy in some cases
      • Stage IIIb
        • Radiochemotherapy
      • Stage IIIc – IV
        • Palliative
        • Any combination of chemo, immune and targeted therapy, depending on histological type and molecular testing
        • Squamous cell carcinoma
          • Polychemotherapy
          • Check for presence of PD-L1, if yes -> pembrolizumab
        • Adenocarcinoma
          • Check for KRAS, EGFR, ROS mutation and ALK/EML4 inversion
          • If KRAS mutation -> chemotherapy
            • KRAS mutation indicates poor prognosis
          • If EGFR mutation -> EGFR inhibitor
          • If ALK/EML4 inversion -> ALK inhibitor
          • If ROS mutation -> ROS inhibitor
  • Small cell lung cancer (SCLC)
    • Accounts for 15% of cases
    • Is a neuroendocrine tumor
    • Has worse prognosis than NSCLC, but is very radio-and-chemosensitive
    • Has a much higher turnover than NSCLC (tumor doubling every 50 days vs 200 days)
    • Associated with paraneoplastic syndromes, like SIADH, Cushing syndrome, etc.
    • Staging
      • Because SCLC is radiosensitive its staging system is based on whether radiotherapy of the tumor is feasible
      • “Limited disease” (corresponds to stages I – IIIB)
        • 20% of cases at diagnosis
        • Cancer spread confined to one hemithorax, and radiotherapy is therefore feasible
      • “Extensive disease”
        • 75% of cases at diagnosis
        • Cancer spread beyond one hemithorax, and radiotherapy is therefore not feasible
    • Treatment
      • Chemotherapy
        • Cisplatin + etoposide
      • Prophylactic cranial irradiation
        • Improves survival by killing brain metastases which are often already present but not visible on scans
      • Limited disease – curative
        • Radiochemotherapy
        • Prophylactic cranial irradiation if remission is achieved
      • Extensive disease – palliative
        • Chemotherapy
        • Prophylactic cranial irradiation in most cases

15. Breast Cancer (BC)

  • Epidemiology
    • Most common cancer in women worldwide
    • 2/3 of cases occur in women 55 or older
  • Etiology
    • Female gender
      • Obviously the biggest risk factor
    • Old age
    • Family history
      • 5 – 10% of cases are hereditary
      • BRCA1 or BRCA2
      • Women with 2 or more first-degree relatives with breast or ovarian cancer have more than 50% risk of developing BC
    • Personal history (women who already have had breast cancer)
    • Certain benign breast conditions
    • Not breastfeeding
      • Breastfeeding lowers BC risk
    • Drinking alcohol
    • Being overweight
    • Physical inactivity
    • Smoking
    • Risk factors which cause increased oestrogen exposure
      • Not having children
      • Early menarche
      • Late menopause
      • Using hormone replacement therapy
  • Genetic testing for hereditary breast cancer is indicated in:
    • Women diagnosed with early stage breast cancer
      • Genetic result will determine the treatment
    • Women with metastatic breast cancer
      • Genetic result will determine the treatment
    • Healthy women who are suspected to have BRCA1 or BRCA2 mutation
      • For example, healthy women with close relatives with breast or ovarian cancer
  • Pathology
    • Histological subtypes
      • Invasive ductal carcinoma – 80% of cases
        • Originates from a milk duct of the breast
      • Invasive lobular carcinoma – 10% of cases
        • Originates from a breast lobule
      • Other – 10% of cases
    • Molecular subtypes
      • Hormone receptor positive or negative
        • Oestrogen receptor and/or progesterone receptor
        • 60% are hormone receptor positive
        • Hormone receptor positivity indicates better prognosis
      • HER2 positive or negative
        • HER2 positivity is due to amplification of the HER2 gene
        • 20 % are HER2 positive
        • HER2 positivity indicates a more aggressive cancer, but because we have targeted therapy against HER2 the prognosis of HER2 positive cancers is the same as HER2 negative
        • Presence of HER2 can be detected by FISH (most accurate) or IHC
      • If all three are negative the cancer is known as “triple negative”
        • 15% are triple negative
        • Triple negativity indicates poorer prognosis
  • Clinical features
    • Many are asymptomatic – screening is important
    • Lump in the breast
  • Stages
    • Early breast cancer
      • Stage 0 – non-invasive
        • Survival 100%
      • Stage 1 – tumour is < 2 cm, no spread
        • Survival 98%
      • Stage 2 – tumour is > 2 cm, may have spread to nearby lymph nodes
        • Survival 93%
      • 30% of early BC relapse into metastatic BC
    • Advanced breast cancer
      • Stage 3 (locally advanced BC) – cancer spread beyond nearby lymph nodes but not to other organs
        • Survival 72%
      • Stage 4 (metastatic BC) – cancer spread to other organs
        • Survival 22%
        • Metastases to bone, brain, liver or lung
  • Diagnosis
    • Mammography
    • Ultrasound of breast and nearby lymph nodes
    • MRI
      • For women with dense breasts, silicone implant or BRCA mutation
    • Biopsy
      • Core needle biopsy, FNAB, or excisional
      • Mandatory for diagnosis
  • Work-up after diagnosis
    • Determination of histological and molecular subtypes
    • Biopsy of suspicious lymph nodes
    • CT chest, abdomen, pelvis
  • Treatment
    • Multidisciplinary teams (oncological teams) are used in the treatment of breast cancer
    • Surgical treatment
      • Some form of surgery is performed in all cases which are operable
      • Mastectomy
        • Radical or modified mastectomy
        • Breast reconstruction can be performed in the same surgery as the mastectomy or at a later point
        • Breast reconstruction can be achieved by implants, by autologous tissue implantation, or both
      • Breast-conserving surgery
        • Sometimes called lumpectomy
        • Must always be followed up by radiotherapy
      • Staging of axillary lymph nodes
        • Must be performed during all surgeries
        • By biopsy or lymph node dissection
    • Radiotherapy
      • Treatment planning is always based on CT to minimize heart and lung radiation
      • The standard is to deliver whole-breast radiation
    • Systemic therapy
      • The molecular subtype determines the systemic therapy
      • Chemotherapy
        • Anthracycline
        • Taxanes
      • Hormonal therapy
        • Hormonal therapy is indicated in most hormone positive patients
        • Selective oestrogen receptor modulators
          • Tamoxifen
        • Aromatase inhibitors
        • Fulvestrant
      • Targeted therapy
        • Anti-HER2
          • For most HER2+ patients
          • Trastuzumab
        • PARP inhibitors
          • For BRCA-positive advanced BC
      • Immune therapy
        • Atezolizumab (PD-L1 inhibitor)
        • For triple-negative breast cancer
    • For early breast cancer (stage 0 – 2)
      • Without BRCA mutation
        • Breast-conserving surgery + adjuvant radiotherapy
      • With BRCA mutation
        • Mastectomy
        • Prophylactic contralateral mastectomy
        • Prophylactic bilateral salpingo-oopherectomy
    • For locally advanced breast cancer (stage 3)
      • Neoadjuvant systemic therapy + surgical resection + adjuvant systemic therapy
    • For metastatic breast cancer (stage 4)
      • The cancer is generally not curable, but it is treatable
      • Neoadjuvant systemic therapy + surgical resection and/or radiotherapy
      • With BRCA mutation – PARP inhibitors

16. Cancer of the oesophagus and the stomach

  • Oesophageal cancer
    • Epidemiology
    • Etiology
      • GERD
      • Smoking
      • Poor diet
      • Obesity
      • Alcohol
    • Pathology
      • Adenocarcinoma
        • Develops from Barrett’s oesophagus
        • Rising incidence
      • Squamous cell carcinoma
        • The most common type, but incidence is declining
      • The absence of tunica serosa in parts of the oesophagus causes oesophageal cancer to metastasize early
    • Clinical features
      • Asymptomatic early
      • Dysphagia
      • Retrosternal pain
    • Diagnosis
      • Oesophageal endoscopy (oesophagogastroduodenoscopy)
        • Best initial and confirmatory test
        • Biopsy can be performed
    • Work-up after diagnosis
      • Endoscopic ultrasound
        • To assess T and N stage
      • CT chest, abdomen
        • To assess M stage
    • Treatment
      • Surgery
        • Endoscopic submucosal resection
          • For very early localized disease
        • Subtotal or total oesophagectomy
          • Most commonly performed surgery
      • Systemic therapy
        • Chemotherapy
          • Commonly used in oesophageal cancer
          • FLOT
        • Targeted therapy
          • Trastuzumab – anti-HER2
        • Immunotherapy
          • Pembrolizumab
      • Radiotherapy
        • Often used with chemotherapy
      • Localized disease
        • Surgery
          • May be sufficient in early localized disease
        • Neoadjuvant chemotherapy or radiochemotherapy
        • Adjuvant chemotherapy
      • Advanced disease
        • Palliative
        • Radiochemotherapy
        • Targeted or immunotherapy
        • Oesophageal stent placement
  • Gastric cancer
    • Epidemiology
      • Male > female
      • Old age
      • High incidence in Korea, Japan
      • Declining incidence in the west
    • Etiology
      • Foods rich in nitrates
      • Salty food
      • Nicotine use
      • Atrophic gastritis
      • H. pylori
      • Gastric ulcers
    • Pathology
      • According to histological cell type
        • Adenocarcinoma (90%)
        • Signet ring cell carcinoma
      • According to the Lauren classification
        • Intestinal type
        • Diffuse type
      • At diagnosis 75% already have metastases
    • Clinical features
      • Often asymptomatic in early stages
      • General signs
        • Iron deficiency anaemia
          • Due to chronic blood loss
        • Weakness
      • Abdominal pain
      • Nausea, vomiting
      • Painful, movable mass in epigastric region
    • Diagnosis
      • Faecal blood test
        • Positive in some cases
      • Gastroscopy (= upper endoscopy) with biopsy
        • Biopsy confirms diagnosis
    • Work-up after diagnosis
      • Endoscopic ultrasound
      • Chest, abdominal and pelvic CT
      • Bone scintigraphy
        • If suspected bone metastasis
      • Laparoscopy
        • If suspected peritoneal carcinosis
    • Treatment
      • Surgery
        • Radical gastrectomy and lymphadenectomy
      • Systemic therapy
        • Chemotherapy
          • FLOT
          • ECX
        • Targeted therapy
          • Trastuzumab – anti-HER2
          • Ramucirumab – anti-VEGF
        • Immunotherapy
          • Pembrolizumab – anti-PD-1
      • Localized disease
        • Surgery
        • Both neoadjuvant and adjuvant chemotherapy or radiochemotherapy are often used
      • Advanced disease
        • Palliative
        • Perioperative chemotherapy + surgery
        • Targeted therapy and immunotherapy are options

17. Cancer of the pancreas and the liver

  • Pancreatic cancer
    • Epidemiology
      • The 10th most frequent cancer, but the fourth leading cause of cancer-related death
    • Etiology
      • Smoking
      • Chronic hepatitis
      • Diabetes
      • Obesity
    • Pathology
      • Responds poorly to chemotherapy
      • Aggressive growth
      • 2/3 in head
      • 1/3 in tail
      • 95% are adenocarcinomas
    • Clinical features
      • Asymptomatic early
      • Belt-like epigastric pain
      • Jaundice
      • Weight loss
      • Trousseau syndrome
        • A paraneoplastic syndrome
        • Causes superficial thrombophlebitis
      • Courvoisier sign
        • Enlarged gallbladder + painless jaundice
    • Stages
      • Resectable disease
        • 15% present in this stage
        • Median survival of 20 – 24 months
      • Locally advanced (unresectable) disease
        • 25% present in this stage
        • Median survival of 8 – 12 months
      • Metastatic disease
        • 50% present in this stage
        • Median survival of 6 – 12 months
      • Overall 5-year survival for all patients is < 5%
    • Diagnosis
      • Abdominal US
        • If positive -> CT with contrast
      • CT with contrast or MRI
        • Sufficient for diagnosis
        • Also provides information for staging
      • Biopsy is required to establish diagnosis
        • However, if there is high clinical suspicion, a biopsy is not necessary
    • Work-up after diagnosis
      • CT chest
      • PET
    • Treatment
      • Surgery
        • Surgery is the only potentially curative treatment
        • “Whipple procedure” (= pancreaticoduodenectomy)
          • If pancreatic head tumour
        • Distal resection
          • If pancreatic body or tail tumour
      • Systemic therapy
        • Chemotherapy
          • Gemcitabine
          • 5-FU
          • Albumin-bound paclitaxel
        • Targeted therapy
          • Erlotinib
      • Radiotherapy
        • Not so frequently used
      • Resectable disease
        • Surgery + adjuvant chemotherapy or chemoradiotherapy
        • If the tumour is borderline resectable -> neoadjuvant chemotherapy
      • Non-resectable disease
        • Palliative treatment
        • Surgery to relieve bile tract obstruction, ileus, etc.
        • Chemotherapy
        • Enrolment into clinical trials
  • Hepatocellular carcinoma
    • Epidemiology
      • Men > women
      • Old age
      • Most common in southeast Asia and Africa
    • Etiology
      • Cirrhosis
        • 80% of HCC cases are preceded by cirrhosis
      • Risk factors independent of cirrhosis
        • Hep B, C
        • Alcohol liver disease
        • Non-alcoholic steatohepatitis
        • Haemochromatosis
        • Aflatoxin
    • Clinical features
      • Usually asymptomatic
        • Patient may have symptoms from underlying disease (cirrhosis, hepatitis)
      • General symptoms
        • Weight loss
        • Weakness
        • Abdominal pain
    • Diagnosis
      • AFP
      • Abdominal US
        • Initial test
        • Focal lesions in a cirrhotic liver are primary liver cancer until proven otherwise
      • Abdominal CT
        • Confirmatory test
      • Liver biopsy
        • Not necessary if definitive diagnosis is established with above tests
        • Carries risk of bleeding and tumor spread
    • Stages
      • Many staging systems for HCC exist, and none are universally accepted
      • It appears that POTE uses the Barcelona Clinic Liver Cancer (BCLC) staging
      • This system stages the cancer based on liver function (Child-Pugh score), patient performance status (ECOG PS) and tumor morphology
      • Liver function is scored according to Child-Pugh score
        • This score checks multiple parameters that reflect liver function and gives points and a final score
          • Child-Pugh A – good liver function
          • Child-Pugh B
          • Child-Pugh C – poor liver function
        • Bilirubin
        • Albumin
        • Prothrombin time
        • INR
        • Presence of ascites
        • Presence of hepatic encephalopathy
      • Very early stage (stage 0)
        • Solitary lesion < 2 cm
        • ECOG PS 0
        • Child-Pugh A
      • Early stage (stage A)
        • Solitary lesion < 2 cm or 3 nodules < 3 cm
        • ECOG PS 0
        • Child-Pugh A or B
      • Intermediate stage (stage B)
        • Multifocal disease
        • ECOG PS 0
        • Child-Pugh A or B
      • Advanced stage (stage C)
        • Portal invasion or extrahepatic spread
        • ECOG PS 1 – 2
        • Child-Pugh A or B
      • Terminal stage (stage D)
        • ECOG PS 3 – 4
        • Child-Pugh C
    • Treatment
      • Targeted therapy
        • Sorafenib
          • Multi protein kinase inhibitor
          • Inhibits VEGFR, PDGFR, RAF, etc.
      • Very early or early stage tumor
        • Surgical resection
      • Early stage tumor
        • Liver transplantation
      • Intermediate stage tumor
        • TACE (transarterial chemoembolization)
      • Advanced stage tumor
        • Sorafenib
      • Terminal stage tumor
        • Palliative care
    • Prevention
      • Patients with high risk for HCC (cirrhosis, hep B or C) should be regularly screening with AFP

18. Colorectal cancer

  • Epidemiology
    • 3rd most common malignancy
    • 2nd most common cause of cancer-related death
    • Average age – 60s
    • 90% of CRC are sporadic, 10% are hereditary
  • Etiology
    • Old age
    • Positive family history
    • IBD
    • Lifestyle factors
      • Smoking
      • Alcohol
      • Obesity
      • Diets high in meat, fat and low in fibre
      • Low level of physical activity
    • Hereditary CRC
      • Familial adenomatous polyposis
        • 100% risk of CRC
        • Germline APC mutation
      • Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
        • 80% risk of CRC
        • DNA mismatch repair gene germline mutation
  • Pathology
    • Most CRC arise from adenomatous polyp
      • Normal epithelium -> hyperproliferation -> adenomatous polyp -> invasive carcinoma
    • Adenocarcinoma accounts for 95% of all CRC
    • RAS, APC, p53 are all involved in carcinogenesis
    • Incidence according to location
      • Right-side colon – 1/4 of cases
      • Left-side colon – 1/3 of cases
      • Rectum – 40% of cases
    • Metastases
      • Colon cancer
        • Mesenteric, paraaortic, retroperitoneal lymph nodes
        • Liver
        • Ovary (Krukenberg tumour)
        • Lung
        • Bone
      • Rectal cancer
        • Pararectal lymph nodes
        • Liver
        • Lung
        • Bone
  • Clinical features
    • Often asymptomatic until late stages
    • General symptoms
      • Weight loss
      • Fatigue
      • Abdominal discomfort
    • Right-sided carcinomas
      • Iron deficiency anaemia
        • Is very suspicious for CRC in elderly and postmenopausal women
      • Melena
    • Left-sided carcinomas
      • Changes in bowel habits
    • Rectum and sigmoid
      • Haematochezia
      • Thin stools
      • Rectal pain
  • Stages
    • Stage I
      • T1 or T2, N0, M0
      • Only invasion of submucosa
    • Stage II
      • T3 or T4, N0, M0
      • Invasion of muscularis propria but N0, M0
    • Stage III
      • Any T, N1 or N2, M0
      • Invasion of subserosa or beyond but M0
    • Stage IV
      • Any T, any N, M1
      • Invasion or visceral peritoneum or adjacent organs
  • Diagnosis
    • Colonoscopy with biopsy
      • Gold standard for diagnosis
      • It is mandatory to survey the whole colon, as multiple cancers may be present simultaneously
    • (Barium enema)
      • May show a filling defect reminiscent of an apple-core
    • (Digital rectal examination)
      • Can only detect 10% of cancers
  • Work-up after diagnosis
    • Transrectal ultrasound – for T and N stage
    • Chest, abdominal and pelvic CT
      • For staging
    • Lab
      • Elevated CA19-9, CEA
    • Histological evaluation
      • Tumour grading
      • Mismatch repair gene mutations
      • HER2 mutation
  • Treatment of colon cancer
    • Surgical therapies
      • Depends on exact localization of tumor
        • Segment resection with intraabdominal anastomosis
        • Rectal extirpation with colostomy
        • Left or right hemicolectomy
      • Lymphadenectomy
        • Always performed, for pathologic staging
      • Resection of metastases in the liver and/or lung
        • One of the few cancers in which it is benificial to resect metastases
    • Chemotherapeutical regimens
      • Chemotherapy
        • FOLFOX
        • FOLFIRI
      • Biological therapy
        • Usually added in stage IV tumors
        • Anti-VEGF – bevacizumab
        • Anti-EGFR – cetuximab/panitumumab
      • Targeted therapy
        • Multi-tyrosine kinase inhibitors like regorafenib
    • Radiation therapies
      • Radiation is not used for colon cancer (or any intraabdominal cancer) because the small bowel is very sensitive to radiation
      • Radiation can be used for rectal cancer, as it lies in the pelvic region
    • Stage I
      • Curative treatment
      • Surgical resection
    • Stage II and III
      • Curative treatment
      • Surgical resection + adjuvant (6 months postoperative) chemotherapy
      • 5-FU or FOLFOX
    • Stage IV
      • Palliative treatment
      • Indicated in bleeding or bowel obstruction
      • Surgical therapy
      • Chemotherapy
      • Biological therapy
  • Treatment of rectal cancer
    • Radiation therapies
      • Radiation can be used for rectal cancer, as it lies in the pelvic region
    • Stage I
      • Curative treatment
      • Surgical resection
    • Stage II and III
      • Curative treatment
      • Neoadjuvant radio-chemotherapy + surgical resection + adjuvant chemotherapy
      • 5-FU
    • Stage IV
      • Palliative treatment
      • Surgical treatment if bleeding or bowel obstruction

19. Non-melanoma skin cancer

  • Etiology
    • UVA and UVB
      • Cumulative, i.e. total sun exposure
  • Pathology
    • UVA causes reactive oxygen species formation
    • UVB
      • Causes direct DNA damage
      • Is more carcinogenic, but most of it is absorbed by the stratosphere
  • Basal cell carcinoma
    • Epidemiology
      • Technically the most common cancer, but it is often excluded from data due to its low mortality and morbidity
      • BCC accounts for 75% of all skin cancer
    • Pathology
      • Hedgehog pathway is often mutated
      • Types
        • Nodular BCC
        • Superficial BCC
        • Morpheaform BCC
        • Naevoid basal cell carcinoma syndrome
          • Autosomal dominant disease
          • Multiple BCC in young age
          • Bone and neurological malformations
        • Etc.
    • Treatment
      • Surgery
        • Surgical excision
        • Primary treatment is almost all cases
      • Radiotherapy
        • If surgery is not an option
      • Chemotherapy
        • Only topical (5-FU)
      • Alternatives for superficial and small BCCs
        • Cryosurgery
        • Photodynamic therapy
        • Laser ablation
        • Topical chemotherapy
        • Topical imiquimod
      • Targeted therapy
        • Vismodegib or sonidegib
          • Hedgehog pathway inhibitors
        • For metastatic BCC or BCC which recurs after surgery
  • Squamous cell carcinoma
    • Epidemiology
      • SCC accounts for 18% of all skin cancer
    • Etiology
      • UV
      • Immunosuppression
        • SCC is the most common cause of death in transplant patients
      • HPV
      • Precursor lesion
        • Actinic keratosis
    • Treatment
      • Surgery
        • Surgical excision
        • Primary treatment is almost all cases
      • Radiotherapy
        • If surgery is not an option
        • As adjuvant therapy if high-risk features are discovered during pathological staging
      • Immune therapy
        • For advanced SCC
        • Cemiplimab – anti-PD-1
      • Alternatives for superficial and small SCCs
        • Cryosurgery
  • Merkel cell carcinoma
    • Cancer development related to immune system dysfunction
      • Higher incidence and worse prognosis in immunocompromised
      • Merkel cell polyomavirus
    • Pinkish nodule on sun-exposed areas
    • Treatment is surgical excision
  • Dermatofibrosarcoma protuberans
    • Rare tumour, but the most common cutaneous sarcoma
    • Translocation between chromosome 17 and 22
    • Treatment is surgical excision
  • Kaposi sarcoma (KS)
    • Etiology
      • Immunosuppression
      • HHV8
    • Types
      • Classic
      • Endemic (in Africa)
      • Associated with non-HIV immunosuppression
      • HIV related
      • Nonepidemic variant
    • Treatment
      • Classic KS -> surgery or radiotherapy
      • HIV-related KS -> treatment of AIDS alone may cause cancer regression
      • KS associated with non-HIV immunosuppression -> changing immunosuppressing drug alone may cause regression

20. Melanoma

  • Epidemiology
    • Melanoma accounts for 5% of all skin cancer
  • Etiology
    • UVA and UVB
      • Especially high doses over short period, in contrast to non-melanoma skin cancer
    • Skin type I and II
    • Sunburns in childhood
    • Precursor lesions
      • Giant (> 20 cm) congenital nevi
      • Lentigo maligna
      • Dysplastic nevi
  • Pathology
    • BRAF mutation is found in 50%
    • Breslow depth, mitotic rate and presence of ulceration on histology are important prognostic factors
    • Types
      • Superficial spreading melanoma
        • 57% of cases
        • Long horizontal spreading phase
      • Nodular melanoma
        • 21% of cases
        • No horizontal spreading phase, just vertical spreading phase
        • Poor prognosis
      • Lentigo maligna melanoma
        • Best prognosis
      • Acral lentiginous melanoma
  • Stages
    • Localized disease – cancer confined to primary site
      • 84% of cases
      • 98% 5-year survival
    • Regional disease – cancer spread to regional lymph nodes
      • 9% of cases
      • 63% 5-year survival
    • Metastatic disease – cancer has metastasized
      • 4% of cases
      • 22% 5-year survival
  • Diagnosis
    • Dermoscope
    • Full-thickness excisional biopsy
      • Removes the entire tumour with a small margin of healthy skin around
      • This is both diagnostic and therapeutic
    • Check for BRAF mutation
  • Treatment
    • Surgery
      • Immediate complete excision is the gold standard
      • A sufficiently large safety margin (1 – 2 cm, depending on Breslow stage) must be used
    • Chemotherapy
      • Not used in melanoma
    • Immunotherapy
      • Checkpoint inhibitors are commonly used in advanced disease
      • Ipilimumab – anti-CTLA-4
      • Nivolumab, pembrolizumab – anti-PD-1
      • Atezolizumab – anti-PD-L1
    • Targeted therapy
      • Vemurafenib – BRAF inhibitor
        • MEK inhibitor (trametinib) is given simultaneously to prevent resistance
    • Localized disease
      • Surgery is often enough
      • Sentinel lymph node biopsy may be performed. If positive -> lymph node dissection and adjuvant immunotherapy or targeted therapy
    • Regional and metastatic disease
      • Surgery + adjuvant immunotherapy and/or targeted therapy

21. Soft tissue sarcomas and bone tumors

22. Nervous system tumors

  • Epidemiology
    • CNS malignancies account for 2% of adult malignancies, but 30% of childhood malignancies
    • CNS metastases occur in 10% of cancer patients
    • Secondary CNS tumours (metastases) are more common than primary
      • Often from lung, breast, melanoma, etc.
    • Most common CNS tumours
      • Meningiomas
      • Glioblastoma
    • Most common in children – medulloblastoma
  • Etiology
    • HIV
    • Nitrosoureas
    • Head irradiation
    • Hippel-Lindau syndrome
    • Recklinghausen syndrome
  • Pathology
    • Location
      • In adults – most tumours are supratentorial
      • In children – most tumours are infratentorial
    • Classification of primary CNS tumours
      • Neuroepithelial tumours
        • Gliomas (most common)
          • Astrocytoma
          • Ependymoma
          • Oligodendroglioma
          • Glioblastoma (grade IV)
        • Embryonal tumours
          • Primitive neuroectodermal tumor (PNET)
          • Medulloblastoma
        • Pinealomas
        • Schwannoma
        • etc.
      • Non-neuroepithelial tumours
        • Meningiomas
        • Tumours of the choroid plexus
        • Germinomas
        • Primary CNS lymphomas
        • Pituitary adenomas
        • etc.
  • Clinical features
    • Seizures
      • Most typical symptom of CNS tumour
    • Focal neurological disturbances
    • Personality changes
    • Headache
    • Vomiting
    • Hypertension (Cushing reflex)
  • Risk factors
    • Grade
      • Most important prognostic factor in CNS tumours
    • Age
    • Performance state
  • Diagnosis
    • Imaging
      • MRI with contrast (best)
      • CT
  • Treatment
    • Neurosurgical intervention
      • Very important in neurooncology because the tumour may have to be removed urgently to reduce symptoms
      • Surgical resection is performed in nearly all CNS tumours
    • Radiotherapy
      • Most brain tumour patients receive some form of radiotherapy, often after surgery as adjuvant therapy
      • External beam radiotherapy is much more common than brachytherapy
      • Advanced techniques like 3DCRT, IMRT and radiosurgery are used to minimize damage to the brain
      • Radiosurgery/stereotactic radiotherapy/gamma knife/Cyber knife therapy
        • Used for lesions smaller than 3 cm
        • Results similar to neurosurgery
      • Craniospinal irradiation
        • For tumours which often spread to CSF, like medulloblastoma
        • The brain and spinal cord are simultaneously irradiated
      • Whole brain radiotherapy (WBRT)
        • Radiation to the whole brain
        • Used for multiple CNS metastases
      • Radiotherapy cause oedema -> increased ICP
        • Prophylactic anti-oedema drugs like steroids, diuretics
    • Chemotherapy
      • Drugs has to penetrate BBB to be eligible for use against CNS tumours
      • Temozolomide
        • Most important drug for CNS tumours
      • BCNU (carmustine)
      • Methotrexate
        • For CNS lymphomas
    • For low-grade (I, II) glioma
      • Neurosurgery alone
    • For high-grade (III, IV) gliomas
      • Neurosurgery (tumour debulking, as complete resection is rarely possible) + radiotherapy + chemotherapy (temozolomide)
    • For primary CNS lymphoma
      • Chemotherapy (methotrexate)
      • Neurosurgery is not used as CNS lymphoma is diffuse rather than localized
    • For meningiomas, mesenchymal tumours, etc.
      • Neurosurgery
      • Radiotherapy in case of unresectable or malignant tumours
    • For secondary brain tumours
      • Solitary tumour – surgery
      • Few metastases – radiosurgery
      • Multiple lesions – whole brain radiotherapy
    • For spinal cord tumours
      • Surgery, sometimes radiotherapy

23. Gynaecologic tumors

  • Ovarian tumors
    • Epidemiology
      • Second most common gynaecological cancer
      • Highest mortality of all gynaecological cancers
      • Primarily a disease of postmenopausal women
    • Etiology
      • Family history
      • BRCA mutation
      • Risk factors which increase oestrogen exposure
        • Early menarche
        • Late menopause
        • Obesity
        • Nulliparity
    • Pathology
      • 90% are epithelial
      • 10% are stromal or germ-cell
    • Clinical features
      • Often produces symptoms late
      • Abdominal pains
      • Ascites
      • Symptoms of metastases into bladder, rectum, etc.
    • Screening
      • No effective screening for general population
      • Screening is only for high-risk women
        • Family history
        • BRCA mutation
      • Pelvic examination twice early
      • Ultrasound
    • Stages
      • Stage I – cancer confined to ovary
        • Rare
      • Stage II – cancer has extended into pelvis
      • Stage III – metastases outside pelvis
        • Most patients are discovered at this stage
        • 20 – 30% 5-year survival
      • Stage IV – distant metastases
      • The staging is pathological, meaning that the findings during exploratory surgery are what determine the stage
      • 70% of cases are discovered in stage III or IV
    • Diagnosis
      • Transvaginal US
        • Gold standard for suspected ovarian cancer
        • Can show the presence of a mass, but cannot distinguish benign from malignant
      • FNAB is never performed as it may cause spreading
      • Diagnosis is generally made during exploratory surgery
      • CA-125 serum marker
    • Work-up after diagnosis
      • CT abdomen and pelvis
      • Vaginal and abdominal US
    • Treatment
      • Surgery
        • Exploratory surgery plays the biggest role in the treatment of ovarian cc and is both diagnostic and therapeutic
        • Surgery always involves:
          • Total extrafascial hysterectomy
          • Bilateral salpingo-oophorectomy
          • Pelvic and para-aortic lymphadenectomy
          • Omentectomy
        • Cytoreduction
          • Performed in stage III, IV, when complete resection of the tumour is impossible
          • Debulking of any lesions suspicious for metastases
        • During the surgery visual assessment of the upper abdomen, peritoneal surfaces, mesentery and other abdominal organs is performed
          • Any abnormal findings are biopsied and intraoperatively examined by a pathologist – if they are metastases, they are debulked
          • This is part of the surgical staging
        • Young, fertile, early-stage patients may receive fertility-preserving surgery instead
          • This involves unilateral salpingo-oophorectomy instead of bilateral, and no hysterectomy
      • Chemotherapy
        • Ovarian cc is chemosensitive
        • Chemo is always used after surgery as adjuvant therapy
          • Except in stage Ia (rare)
        • Paclitaxel + cisplatin/carboplatin
      • Targeted therapy
        • Bevacizumab
      • Radiotherapy
        • Rarely used due to low radiosensitivity
        • Sometimes as palliative treatment
      • Stage I – II
        • Complete resection during exploratory surgery + adjuvant chemotherapy
      • Stage III – IV
        • Cytoreduction during exploratory surgery + adjuvant chemotherapy
    • Follow-up
      • Tumor marker CA-125 is used for follow-up
    • Prognosis
      • High incidence, high mortality
      • High rate of recurrence
      • Prognosis in stage III, IV depends on the degree of cytoreduction which is achieved
  • Cervical cancer
    • Etiology
      • HPV 16, 18, 31, 33
      • Smoking
      • HIV
    • Pathology
      • Originates from the squamocolumnar junction
      • 90% squamous cell
        • Originate from the surface of the cervix (ectocervix)
      • 10% adenocarcinoma
        • Originate from the endocervix
        • Worse prognosis than squamous
      • Very rare
        • Clear cell
        • Small cell
    • Clinical features
      • Asymptomatic in early stages
      • Abnormal vaginal discharge or bleeding
    • Stages
      • FIGO staging system
      • Early cervical cancer
        • Cancer which has not invaded the parametrium
        • Includes stages Ia, Ib, IIa
      • Locally advanced cancer
        • Cancer which has invaded the parametrium
        • Includes stages IIb and III
      • Metastatic cancer
        • M1
        • Stage IV
      • CT or MRI for staging
    • Screening
      • With pap smear
      • Annually after sexually active age
      • Low risk patients who has had two successive negative smears can perform it less frequently
    • Diagnosis
      • Pap smear
        • High specificity but moderate sensitivity
        • Scraping of ectocervix and endocervix with spatula or brush
        • Also used for screening
      • Colposcopy with biopsy
        • Excisional biopsy (conization)
    • Work-up after diagnosis
      • Imaging
        • CT, MRI, PET
      • Bimanual examination
        • One finger in vagina and one finger in anus
        • Used to palpate for spreading to parametrium
      • Creatinine and urea
        • Cervical cc can invade the ureters, causing kidney injury
        • Cisplatin is nephrotoxic, so knowing the status of the kidney before therapy is important
      • CT chest, abdomen, pelvis
      • MRI pelvis
    • Treatment
      • Surgical
        • Conservative surgery
          • Extrafascial hysterectomy without pelvic adenectomy
        • Wertheim operation
          • Modified radical hysterectomy + pelvic lymphadenectomy
          • Total removal of uterus and its ligaments
          • Removal of pelvic lymph nodes on both sides
      • Radiation
        • Radiation is very effective in all stages of cervical cc
        • External beam radiation therapy (EBRT)
          • The bladder is sensitive to radiation, so external radiation for cervical cancer should be limited to 50 Gy
          • After 50 Gy has been delivered by ERBT, we switch to brachytherapy
        • HDR brachytherapy with afterloading
      • Chemotherapy
        • Not often used in early cervical cancer
        • Often used in combination with radiotherapy
        • Cisplatin
          • Most commonly used chemotherapy in cervical cc
        • 5-FU sometimes added
      • Microinvasive cervical cancer
        • Corresponds to stage Ia1
        • Conservative surgery
      • Early cervical cancer
        • No invasion of parametrium
        • Wertheim operation or radiation
        • Both surgery and radiation have equal probability of cure but different morbidity
        • Postoperative radiochemotherapy, if features that signify high risk for recurrence are discovered during the surgery, like
          • Lymph node spread
          • Positive surgical margins
          • Invasion into parametrium
          • Other high-risk features
      • Locally advanced cervical cancer
        • Invasion of parametrium
        • Radiochemotherapy
        • Surgery is not used
      • Stage IVb or recurrent cc
        • Palliative treatment, if there are symptoms like pelvic pain, bleeding
        • Radiotherapy or systemic therapy
  • Endometrial cancer
    • Epidemiology
      • Most common gynaecological cancer
      • Primarily occurs in postmenopausal women
    • Etiology
      • Unopposed oestrogen
        • Obesity
        • Nulliparity
        • Infertility
      • Diet
      • Diabetes
      • Hypertension
      • Tamoxifen treatment
    • Pathology
      • Type I – endometrioid type
        • In 80% of cases
        • Grows slowly
        • Hormone-sensitive
        • Good prognosis
      • Type II – other types
        • Not hormone sensitive
        • Not from endometrium
        • Poor prognosis
    • Clinical features
      • Early signs and symptoms
        • Screening is not needed
      • Vaginal discharge
      • Abnormal vaginal bleeding
    • Stages
      • Stage I – cancer confined to the uterus
        • 72% are diagnosed at this stage
      • Stage II – cancer has spread to cervix
      • Stage III – cancer has spread beyond uterus but still only in the pelvis
      • Stage IV – distant metastases
        • 3% are diagnosed at this stage
    • Diagnosis
      • Fractional dilatation and curettage -> histology
        • Gold standard for any abnormal bleeding
    • Work-up after diagnosis
      • MRI abdomen, pelvis
      • Chest X-ray
    • Treatment
      • Surgery
        • Total abdominal hysterectomy (TAH) with bilateral salpingo-oopherectomy
          • Pelvic and para-aortic lymphadenectomy may also be performed
        • Performed in all cases where possible
        • The majority of patients with endometrial cancer present with early stage cancer, which is curable with surgery alone
        • During the pathological staging, the cancer will be staged as low, intermediate or high-risk for persistence or recurrence, based on factors like
          • High tumour grade
          • Deep myometrial invasion
          • Lymph node involvement
          • etc.
        • Low-risk disease does not require adjuvant therapy
          • Surgery alone is curative in most low-risk patients
        • Intermediate-risk disease will be treated by postoperative (adjuvant) radiotherapy
        • High-risk disease will be treated by postoperative (adjuvant) chemotherapy
      • Radiotherapy
        • Compared to cervical cancer, endometrial cancer is not so sensitive to radiotherapy
        • Primary radiotherapy (without surgery) is reserved for inoperable or palliative patients
        • Both external beam radiotherapy and intravaginal brachytherapy are used
      • Chemotherapy
        • Not commonly used in endometrial cancer
        • Platinum-based drugs
      • Hormonal therapy
        • Progestins are the most commonly used hormonal agents
      • Stage I and II
        • Surgery (+ postoperative radiotherapy)
        • Some patients with stage I may be candidates for hormonal therapy only, which preserves fertility
          • Hormonal therapy is less effective than surgery, however
      • Stage III and IV
        • Treatment is often palliative
        • Cytoreductive surgery when feasible
          • Cytoreductive surgery increases survival
        • Any combination of chemo, radio or hormonal therapy

24. Urologic and male genital cancers

  • Prostate cancer
    • Epidemiology
      • The lifetime risk of prostate cancer is 1 in 8
      • 64% of men between 60 and 70 have it
    • Metastases
      • Bone
      • Liver
      • Bladder
    • Risk groups
      • The risk for progression to metastatic disease is based on the following factors:
      • TNM Stage
      • Gleason score
      • PSA level
    • Diagnosis
      • PSA
        • New ways to measure PSA may increase the specificity of PSA for prostate cancer
          • Free to total PSA radio
          • Complexed PSA
          • [-2]proPSA percent
          • PSA velocity
          • PSA density
        • PSA is also used for follow-up
      • Biopsy
        • For definitive diagnosis
        • Transurethral, transrectal or transperineal
    • Work-up of diagnosed prostate cancer
      • Histopathological examination of biopsy
        • Grading according to the Gleason score
          • Gleason 2 – 6 = low grade
          • Gleason 7 = intermediate grade
          • Gleason 8 – 10 = high grade
      • MRI
      • Bone scan
        • If high grade
    • Progression of localized prostate cancer
      • If cancer is not completely cured during the primary treatment, it will relapse
      • Relapsed cancer is often treated with hormone therapy
      • Hormone therapy initially helps, as the cancer at this stage is hormone-naïve or castrate-sensitive prostate cancer (CSPC)
      • After some time, however, hormone therapy loses its efficacy. The cancer has become castration-resistant prostate cancer (CRPC)
        • At this point the testosterone levels are still at castration levels, but the tumour has grown independent of testosterone
        • This doesn’t mean that hormone therapy is useless
        • CRPC is often metastatic
    • Treatment
      • Observational strategies
        • Many cases of prostate cancer are better left untreated
        • Watchful waiting
        • Active surveillance
      • Surgery
        • Radical prostatectomy
        • Pelvic lymphadenectomy may be performed
      • Radiotherapy
        • Prostate cancer requires a very high load of radiation for local control, up to 100 Gy total
          • For this reason, EBRT and brachytherapy are often combined
        • External beam radiation therapy
        • Brachytherapy
          • HDR or seeding
      • Systemic therapy
        • Hormonal therapy
          • Androgen deprivation therapy (ADT)
            • Orchiectomy (surgical castration)
            • GnRH agonists or antagonists (chemical or pharmacological castration)
          • Antiandrogens
            • Never given alone – always combined with castration
            • Abiraterone – testosterone synthesis inhibitor
            • Enzalutamide – androgen receptor antagonist
          • Side effects of hormonal therapy
            • Erectile dysfunction
            • Osteoporosis
            • Metabolic syndrome
            • Cognitive loss
        • Chemotherapy
          • Docetaxel or other taxanes
          • Used only in castrate-resistant metastatic disease
        • Immunotherapy
          • Sipuleucel-T (a cancer vaccine)
        • Bone-targeting therapy
          • In cases of bone metastases
          • Bisphosphonates
          • Denosumab
          • Radium-223
            • This isotope mimics calcium and so is incorporated into areas of bone where bone metastases are forming
      • Low-risk and intermediate-risk localized disease
        • Observational strategies
        • Surgery or radiotherapy
      • High-risk localized and locally advanced disease
        • ADT + ERBT or surgery
      • Metastatic disease
        • Hormone-naive
          • ADT + antiandrogens
        • Castration-resistant
          • ADT + antiandrogens + chemo/immunotherapy
          • Radium-223 is often used due to bone metastases
  • Bladder cancer
    • Epidemiology
      • Most common cancer of the urinary system
    • Etiology
      • Smoking
    • Pathology
      • Urothelial carcinoma
        • Most common
      • Squamous cell carcinoma
        • Associated with schistosomiasis, chronic UTI and indwelling catheters
    • Clinical features
      • Painless gross haematuria
        • Most common
      • Irritative voiding symptoms
        • Dysuria
        • Increased frequency
        • Urinary urgency
    • Stages
      • Non-muscle invasive bladder cancer (NMIBC) = stage I
        • Ta, T1 or Tis
      • Muscle-invasive bladder cancer (MIBC) = stage II, III
        • T2, T3, T4
      • Metastatic bladder cancer = stage IV
        • M1
    • Diagnosis
      • Urine cytology
      • Cystoscopy
        • Often combined with photodynamic diagnostics (PDD), which causes tumour cells to fluoresce
        • Simple biopsies can be taken
      • Transurethral resection of bladder tumour (TUR-B)
        • Both diagnostic and therapeutic
        • In all (non-metastatic) bladder cancers it’s important to know whether the cancer has invaded the muscular layer or not, which only TUR-B can tell
    • Work-up after diagnosis
      • If the cancer isn’t muscle-invasive, no further work-up is necessary
      • CT urography
        • These cancers are often multifocal, so the entire urinary tract must be examined
      • CT abdomen and pelvis
    • Treatment
      • Surgery
        • Transurethral resection of bladder tumour (TUR-B)
          • The tumour and some surrounding bladder tissue are removed with a transurethral resectoscope
          • This is both diagnostic and therapeutic
          • After the resection, chemotherapeutical drugs or BCG are instilled into the bladder to reduce any residual cancer cells
        • Radical cystectomy
        • Bladder preservation therapy
          • (Extensive) TUR-B followed by radiochemotherapy
          • An alternative to radical cystectomy which preserves the bladder
      • Radiotherapy
        • Inoperable tumours
        • As part of bladder preservation therapy
      • Systemic therapy
        • Chemotherapy
          • Gem/cis
        • Immunotherapy
          • Atezolizumab (anti-PD-L1)
          • Pembrolizumab (anti-PD-1)
        • BCG vaccine
          • Intravesical BCG helps the immune system kill urothelial cancer
      • Non-muscle-invasive bladder cancer
        • TUR-B alone is often enough
        • Intravesical BCG or chemo is instilled after TUR-B
      • Muscle-invasive bladder cancer
        • Radical cystectomy or bladder preservation therapy
      • Metastatic bladder cancer
        • TUR-B is not performed
        • Palliative
        • Chemotherapy or immunotherapy
  • Renal cell carcinoma (RCC)
    • Etiology
      • Smoking
      • Obesity
      • Family history
    • Pathology
      • These are adenocarcinomas which arise from tubular epithelium
        • Urothelial cancers of the renal pelvis (etc.) don’t count as RCC
      • 80 – 90% are clear cell carcinoma
      • 10 – 15% are papillary carcinoma
    • Clinical features
      • Mostly asymptomatic
        • 50% are incidental findings on imaging
      • Haematuria
      • Anaemia
      • Palpable flank mass
      • Paraneoplastic syndromes
    • Stages
      • T1 – tumour < 7 cm
      • T2 – tumour > 7 cm
      • T3 – Tumour extends into renal vein or perinephric tissues
      • T4 – Tumour extends beyond Gerota fascia
    • Risk groups
      • The risk for progression to metastatic disease is based on the following factors:
      • TNM stage
      • Tumour size
      • Presence of histological necrosis
      • Tumour grade
      • Abnormal labs (LDH, Hb, Plt, etc.)
    • Diagnosis
      • CT abdomen with contrast
    • Work-up after diagnosis
      • CT/MRI thorax
    • Treatment
      • Surgery
        • Nephron-sparing surgery (= partial nephrectomy)
          • Preferred, when feasible
        • Radical nephrectomy
      • Radiotherapy
        • Stereotactic radiotherapy
        • For inoperable patients
      • Systemic therapy
        • Targeted therapy
          • Anti-VEGF
            • Bevacizumab
          • mTOR inhibitors
            • Everolimus
          • Tyrosine kinase inhibitors
            • Sunitinib, sorafenib, etc.
            • Cabozantinib
            • Pazopanib
        • Immunotherapy
          • Nivolumab (anti-PD-1)
          • Ipilimumab (anti-CTLA-4)
      • Localized disease
        • Surgery
      • Metastatic disease
        • Low or intermediate risk -> targeted therapy
        • High risk -> immunotherapy
  • Testicular cancer
    • Epidemiology
      • Most common cancers in men 15 – 35
      • Surprisingly rare in women
    • Etiology
      • Cryptorchidism
      • Klinefelter syndrome
    • Pathology
      • Seminomas (50%)
        • Very radiosensitive
      • Non-seminomas (50%)
        • Often a combination of embryonal carcinoma, yolk sac, choriocarcinoma, etc.
        • Moderately radiosensitive
    • Clinical features
      • Mostly asymptomatic
      • Testicular lump
    • Stages
      • Limited disease – cancer limited to testicles
      • Locally advanced disease – retroperitoneal lymph node involvement
      • Metastatic disease – M1
    • Diagnosis
      • Testicular ultrasound
        • Often enough to establish the presence of malignant tumour
      • Tumor markers
        • LDH
        • hCG
        • AFP
      • Orchidectomy
        • Both diagnostic and therapeutic
    • Work-up after diagnosis
      • CT chest, abdomen, pelvis
    • Treatment
      • Surgery
        • Radical (inguinal) orchidectomy
          • Performed in all cases
        • Retroperitoneal lymph node dissection (RPLND)
          • Para-aortic lymph nodes are most commonly affected
      • Radiotherapy
        • External beam radiotherapy
        • Generally only used in seminomas, not non-seminomas
        • Radiotherapy is less and less used, chemo is more and more preferred instead
      • Chemotherapy
        • Cisplatin
        • Etoposide
        • Bleomycin
      • Localized disease (stage I)
        • Orchidectomy
        • Active surveillance
          • In low-risk localized disease
        • Adjuvant chemotherapy
          • In intermediate and high-risk localized disease
      • Locally advanced disease (stage II)
        • Orchidectomy + adjuvant radio (targeting retroperitoneal lymph nodes) or polychemotherapy or RPLND
      • Metastatic disease (stage III)
        • Orchidectomy + polychemotherapy

3 thoughts on “Oncology”

  1. Hello 🙂 I think the Krukenberg tumor is arising from gastric ccs only, not CRC as you put in the topic (not 100% sure)

    1. That is in fact not correct, Krukenberg can arise from anywhere but classically from gastric cancer.

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